Objective To investigate the early diagnostic value and cost‐effectiveness analysis of common inflammatory markers , including interleukin‐6 (IL‐6 ) , procalcitonin (PCT ) and C‐reactive protein (CRP) in cirrhotic patients with infectious fever .Methods From January 2012 to January 2015 , cirrhotic patients hospitalized in liver center of First Affiliated Hospital ,Fujian Medical University who were excluded with community‐acquired infections and developed fever 48 hours after admission were selected .According to having infection or not ,they were divided into infection group and non‐infection group .White blood cell count (WBC) ,neutrophil percentage (N % ) ,IL‐6 ,PCT ,and CRP at admission (baseline) and at the time point of fever were recorded .The diagnostic threshold of WBC ,N% ,IL‐6 , PCT ,and CRP for infectious fever in cirrhotic patients were analyzed by receiver operating characteristic analysis curve (ROC) .The cost‐effectiveness (C/E) of those biomarkers were compared .Results A total of 299 cases were enrolled ,with 162 in infection group and 137 in non‐infection group .Two hundred and forty‐four were male and 55 were female .The mean age was 55 .1 ± 13 .0 years .Upon the onset of fever , WBC ,N% ,IL‐6 ,PCT ,and CRP of infection group were all significantly higher than those of non‐infection group (all P< 0 .05) .The area under the curve of IL‐6 for infectious fever was 0 .939 (95% CI 0 .910 - 0 .968) ,which was significantly higher than those of PCT and CRP (Z = 5 .718 and 9 .048 , respectively ,both P< 0 .01) .The optimal cut‐off point of IL‐6 was 184 .5 ng/L ,with the sensitivity of 85 .2% and specificity of 94 .9% .C/E value was 38 .3 for N% ,and 51 .2 for CRP . However ,both specificity and specificity of CRP and N % were low .C/E value was 389 .0 for PCT and 63 .4 for IL‐6 .IL‐6 had the highest sensitivity (85 .2% ) and specificity (94 .9% ) among all the biomarkers .Conclusions Compared to PCT and CRP ,IL‐6 has the highest sensitivity and specificity with lower cost‐effectiveness for diagnosis of infectious fever in cirrhotic patients .

The incidence rate of hepatocellular carcinoma (HCC) is increasing around the world and tends to decrease in East Asia and several regions in China;however, China still has higher incidence rate and mortality rate of HCC than most countries.Studies have shown that long-term antiviral therapy can inhibit HBV replication to a very low level or help patients with HCV infection achieve sustained virologic response, which can further reduce the incidence rate of virus-related HCC.New evidence suggests that compared with nucleos(t)ide analogues, PEG-IFNα has a better effect of secondary prevention.Studies also indicate that interferons play an important role in tertiary prevention of virus-related HCC.This article reviews the epidemiological studies on virus-related HCC in recent years and the role of antiviral therapy in second and tertiary prevention and points out that adequate and effective antiviral therapy is the basis for preventing the development and recurrence of HCC.

Aim To purify monoclonal antibody in mouse ascites by a modified membrane affinity chromatography(MAC). Methods Human serum albumin HSA was adsorbed on the zeta-bind membrane (ZBM), a positively charged nylon membrane filter. Then the mouse aecites containing mAbs were filtrated through the ZBM to cause the mAbs bind to HSA adsorbed on ZBM. Finally,the purified mAbs were dissociated from the ZBM with guanidine hydrochloride solution. Results A sheet of ZBM(diameter 50mm) absorbed with HSA filtrated by 10 mL ascites could reach its maximum mAb binding capacity after two rounds of re-fitration. The dissociation of mAb from ZBM need only one round of filtration of dissociating solution. The purified mAb displayed a single band after PAGE. Sensitivity of detedcting HSA with purified mAbs was 20-fold higher than that with unpurified ascites in dot innunogold filtration assay(DIGFA). Conclusion The modified MAC with ZBM is a much easier, time-saving and effective method for affinity purification of antibodies in ascites.

Objective To improve the method of abdominal transplantation of hepatocytes. Methods The rat hepatic cells were embedded in collagen gel and cultured in vitro. The total protein (TP) and BUN levels in the nutrient solution were measured. The mixture of collagen nutrient solution and the hepatocytes was injected into abdominal cavity of rat recipients and then turned to gel there, so the hepatocytes were embedded in the gel. The hepatocytes in the abdominal cavity were rinsed out by the nutrient solution containing collagenase and were cultured in vitro in the nutrient solution without glucose (Glu). The Glu levels in the nutrient solution were measured. The control groups underwent the same process as the experimental groups except collagen. Results The TP, BUN and Glu levels in the experimental groups (hepatocytes embedded in collagen gel) were significantly higher than those in the control groups ( P

Objective To identify the predictive factors associated with hepatitis B surface antigen (HBsAg) loss in hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) patients treated with pegylated interferon (PEG-IFNα-2a).Methods Seventy-two HBeAg positive CHB patients were treated with PEG-IFNa-2a 180 μg weekly for 48 weeks. The serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and hepatitis B virus (HBV) DNA,HBeAg, and HBsAg were quantitatively detected every 3 months. The relationship between HBV DNA, HBeAg, and HBsAg levels at baseline, week 12, 24 of treatment and HBsAg loss was analyzed.The data were statistically assessed by Fisher's exact test,and receiver operating characteristic (ROC) curve. ResultsTotally 65 patients accomplished the therapy, and 7 (10.8％)patients achieved HBsAg loss. HBsAg loss at week 48 of treatment was associated with HBeAg level at week 12 of treatment (Fisher's exact test, P= 0. 023), HBeAg level at week 24 (Fisher's exact test, P=0. 004), and lower HBsAg levels (＜250 IU/mL) at week 12 and 24 of treatment (Fisher's exact test,P=0. 001 and 0.002, respectively). HBsAg loss was associated with HBV DNA negative ( ＜ 1000 copy/mL) at week 12 of treatment (Fisher's exact test, P = 0. 039), while not associated with HBV DNA negative at week 24 of treatment (Fisher's exact test, P=0. 130). ROC curve analysis revealed that the AUC was 0. 8584(P=0. 0021) of HBsAg level at week 12, 0. 9606(P=0. 001) of HBsAg level at week 24, and 0. 8350(P=0. 040) of HBeAg level at week 24. ConclusionLevels of HBsAg and HBeAg at week 24 of treatment might serve as effective factors to predict HBsAg loss in patients received PEG-IFN monotherapy.

Objective To investigate risk factors for hepatic steatosis in patients with chronic hepatitis B (CHB). Methods One hundred and eighty patients with biopsy-proven chronic hepatitis B were included in the study. Those with liver steatosis (61 from 93 cases) and those without it (61 from 87 cases)were matched on gender and age ( ± 3 years). Results Body mass index (BM I) was significantly higher in case group (24 ±3) than that in controls (22 ±3) (P ＜0.01 ). No significant difference was found in fasting plasma glucose, total cholesterol, triglycerides, urine acid, alanine aminotransferase, glutamyl transpeptidase and hepatitis B virus ( HBV ) DNA between the cases and controls ( all P ＞ 0. 05 ).Conditional logistic regression analysis with proportional hazard regression model statement by SPSS software showed that BMI was the only independent correlate to liver steatosis in patient with CHB ( OR = 1. 488, P ＜0. 01 ). Conclusions Liver steatosis in patients with CHB associates with BMI of the hosts, but does not correlate to their HBV DNA level.

Objective To investigate the correlation between non-alcoholic fatty liver disease and serum and histological viral parameters in patients with chronic hepatitis B (CHB).Methods Clinical and laboratory data from patients with CHB who received liver biopsy from 2009 to 2015 were collected. Patients were divided into steatosis and non-steatosis groups based on the presence of steatosis in liver biopsies.Propensity score matching (PSM)was conducted to adjust the confounding bias including age, sex,body mass index (BMI),total cholesterol (TC)and triglyceride (TG).Correlation of liver fatty and viral parameters was compared between steatosis and non-steatosis groups.Student t test,χ2 test,rank sum test and Pearson correlation test were employed to analyze the data.Results A total of 874 patients with a mean age of (37.0±10.1)years were enrolled in the study,with 690 males and 184 females,and 270 (30.9%)patients were diagnosed with steatosis by liver biopsy.Age,gender,BMI,TC and TG were significantly different between the two groups before PSM (all P <0.05),but those were comparable after PSM (all P >0.05 ).Serum hepatitis B virus (HBV)DNA,hepatitis B surface antigen (HBsAg) level,proportion of hepatitis B e antigen (HBeAg )positivity,HBsAg and hepatitis B core antigen (HBcAg)immunohistological staining in liver tissue were not significantly different between steatosis and non-steatosis groups after PSM (all P >0.05).Patients in steatosis group were stratified into two groups according to the degree of steatosis confirmed by liver biopsies:mild steatosis group (F1 )and medium to severe steatosis group (F2-F4).The serum alanine aminotransferase (ALT),HBV DNA,HBsAg level, proportion of HBeAg positivity,immunohistological HBsAg and HBcAg staining in liver tissue between those two groups showed no differences (all P >0.05).The mean rank of liver inflammation and fibrosis in F1 group were 129.9 and 128.2,respectively,which were both significantly higher than those in F2-F4 group (105 .9 and 108.5 ,respectively;both P <0.05).Steatosis was negatively correlated with either inflammatory grade (r=-0.183,P =0.005)or fibrosis stage (r=-0.150,P =0.020).Conclusions There is no correlation between serum viral factors and hepatic steatosis. Hepatic steatosis is not associated with the expressions of HBsAg and HBcAg in liver tissue.The severity of steatosis is negatively correlated with both liver inflammation and fibrosis.

Objective To investigate the relationship between serum HBeAg level and inflammation grade (G)/fibrosis stage (S) in the liver tissues of chronic hepatitis B (CHB) patients in the immune clearance phase (IC). Methods Both liver biopsy samples and serum samples were consecutively collected from CHB patients in Liver Center,First Affiliated Hospital,Fujian Medical University during March 2007 to June 2010.Electro-chemiluminescence and fluorogenic quantitative polymerase chain reaction (PCR) methods were used to determine HBeAg titer and hepatitis B virus (HBV) DNA level,respectively.The relationships between HBeAg titer and liver pathological stages were analyzed using Spearman rank correlation analysis.Receive operating characteristic (ROC) curve was used to evaluate the diagnostic value of HBeAg for liver pathological stages.Results Totally 249 patients with CHB were enrolled into this study.The serum HBeAg absorbances in patients with liver inflammation G1 to G4 were (2.93±2.85),(2.96±2.74),(2.69±2.67) and (2.30±2.41) lg s/co,respectively,while those in patients with liver fibrosis S1 to S4 were (2.99±2.74),(2.89±2.73),(2.58±2.55) and (2.32±2.44) lg s/co,respectively,which indicated that serum HBeAg titers were significant different in patients with different grading and staging of liver tissues (x2 =47.13,P＜0.01; x2 =74.12,P＜0.01).Spearman rank correlation analysis showed that serum HBeAg titer was negatively correlated with inflammation grades and fibrosis stages of liver tissues (r=-0.418 and-0.532,respectively; both P＜0.01).ROC curve analysis revealed that the areas under the curve (AUC) were 0.74 (G≥≥3) and 0.73 (G≥4),and the HBeAg (s/co) cut-off values were 2.95 and 2.64 lg s/co,respectively.Similarly,ROC curve analysis revealed that the AUC were 0.80 (S≥3) and 0.77 S≥4),and the HBeAg cut-off values were 2.99 and 2.82 lg s/co,respectively.Conclusions The serum HBeAg titer is negatively correlated with the inflammation grades and fibrosis stages m liver tissues of CHB patients in IC phase.The level of HBeAg may be used as an adjunctive noninvasive marker to reflect the inflammation and fibrosis status in the liver.

OBJECTIVE: To investigate the factors that influence the curative effect in patients with HBeAgpositive chronic hepatitis B (CHB) treated with peg-interferon α-2a, and to explore whether such factors might predict the therapeutic effect. METHODS: HBeAg-positive CHB patients treated with peg-interferon α-2a (180 μg once a week) were divided into a standard therapy group (48 weeks) and an extended therapy group (>48 weeks). The rates of HBsAg loss, HBeAg loss, HBeAg seroconversion, HBV DNA clearance, and ALT normalization were all evaluated in the two groups at the end of treatment and after 24 weeks follow up. RESULTS: A total of 81 patients were enrolled in the study. The standard therapy group included 37 patients, and the extended therapy group included 44 cases, with durations ranging from 52 to 92 (median 72) weeks. The baseline clinical data were comparable between the two groups (P>0.05). At the end of treatment and at 24 weeks of follow-up, the HBeAg seroconversion rate of the extended therapy group was significantly higher than that of the standard therapy group (54.5% vs 29.7%, P=0.025, at 24 weeks; 76.9% vs 52.9%, P=0.008, after follow-up). In the standard therapy group, age and half-quantification of HBeAg at 24 weeks of treatment were the predictive factors for HBeAg seroconversion at 24 weeks of follow-up. Using a logistic regression model, the area under the receiver operating characteristic curve was 0.872, taking the optimum cut-off point of -1.299, with 100.0% sensitivity at 66.7% specificity. COX multi-factor analysis (of the two groups) showed that age and therapy duration were predictive factors for HBeAg seroconversion at 24 weeks of follow-up. CONCLUSION HBeAg-positive CHB patients treated with peg-interferon α-2a may have a better curative effect at a young age or with extended therapy. Age and half-quantification of HBeAg at 24 weeks of treatment may predict HBeAg seroconversion at 24 weeks of follow-up after completion of the standard therapy.
Adult ; Age Factors ; Antiviral Agents ; therapeutic use ; Female ; Hepatitis B Surface Antigens ; blood ; Hepatitis B e Antigens ; blood ; Hepatitis B, Chronic ; drug therapy ; virology ; Humans ; Interferon-alpha ; therapeutic use ; Male ; Polyethylene Glycols ; therapeutic use ; Recombinant Proteins ; therapeutic use ; Treatment Outcome ; Young Adult

Objective T he present study aimed to optimize the established predictive models (REACH‐B scoring model) for hepatitis B virus (HBV)‐related hepatocellular carcinoma (HCC) . Methods The hepatitis B surface antigen (HBsAg) positive (> 6 months) patients who were firstly admitted in the Liver Center of First Affiliated Hospital ,Fujian Medical University between Oct 1st 2004 and May 1st 2014 were selected as the subjects and divided into two groups ,namely ,the case group (HCC group) and the control group (non‐HCC group) .Clinical data of all the subjects were retrospectively collected and analyzed .Receiver operating characteristic curves were used to evaluate the predictive values of the various models .Results To predict the development of HBV‐related HCC within 3 years ,a total of 627 patients (151 HCC cases and 476 non‐HCC controls) were enrolled .Area under curve (AUC) of HBV‐related HCC (REACH‐B) scoring model was 0 .78 (95% CI:0 .74-0 .82) ,with the sensitivity of 73 .00% and specificity of 78 .70% in predicting 3‐year risk of HCC occurrence .By combining alpha‐fetoprotein (AFP) and REACH‐B ,the R‐AFP scoring model was constructed .The AUC increased to 0 .80 (95% CI:0 .76 -0 .83 , Z= 2 .50 , P= 0 .01) ,with the sensitivity of 71 .03% and specificity of 79 .13% in predicting 3‐year HCC development .By combining AFP isoform 3 (AFP‐L3% ) and REACH‐B ,the R‐AFP‐L3% scoring model was constructed .The AUC further increased to 0 .83 (95% CI:0 .80-0 .87 ,Z=2 .45 ,P=0 .01) ,with the sensitivity of 75 .01% and specificity of 79 .32% in predicting 3‐year HCC development .To predict the development of HBV‐related HCC within 5 years ,a total of 159 (65 HCC cases and 94 non‐HCC controls) were enrolled .The AUC of REACH‐B scoring model was 0 .79 (95% CI:0 .72-0 .87) ,with the sensitivity of 73 .60% and specificity of 75 .43% .The R‐AFP scoring model had an AUC of 0 .84 (95% CI:0 .77-0 .90 ,Z=2 .70 ,P=0 .006) ,with the sensitivity of 83 .12%and specificity of 77 .89% .Conclusion Combination of AFP or AFP‐L3% may optimize the predictive values of REACH‐B scoring model in predicting 3‐year and 5‐years risks of developing HBV‐related HCC .